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Q05921 (RN5A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
2-5A-dependent ribonuclease

Short name=2-5A-dependent RNase
EC=3.1.26.-
Alternative name(s):
Ribonuclease 4
Ribonuclease L
Short name=RNase L
Gene names
Name:Rnasel
Synonyms:Rns4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length735 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. Might play a central role in the regulation of mRNA turnover By similarity. Ref.3

Catalytic activity

Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length.

Cofactor

Manganese or magnesium. Required for optimal RNA cleavage rates.

Enzyme regulation

After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family By similarity.

Subunit structure

Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL By similarity.

Subcellular location

Cytoplasm. Mitochondrion Ref.3.

Tissue specificity

Expressed in spleen, thymus, lung, testis, kidney, liver and heart.

Induction

By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL.

Domain

The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain.

The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization.

The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity.

Sequence similarities

Belongs to the protein kinase superfamily.

Contains 9 ANK repeats.

Contains 1 KEN domain.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 7357352-5A-dependent ribonuclease
PRO_0000067052

Regions

Repeat24 – 5330ANK 1
Repeat58 – 8730ANK 2
Repeat91 – 12030ANK 3
Repeat124 – 15330ANK 4
Repeat167 – 19731ANK 5
Repeat201 – 23434ANK 6
Repeat238 – 26831ANK 7
Repeat272 – 30130ANK 8
Repeat303 – 32826ANK 9
Domain364 – 584221Protein kinase
Domain587 – 722136KEN
Zinc finger401 – 43636C6-type Potential
Region229 – 242142-5A binding (P-loop) 1
Region253 – 275232-5A binding (P-loop) 2

Sequences

Sequence LengthMass (Da)Tools
Q05921 [UniParc].

Last modified February 11, 2002. Version 2.
Checksum: B6632F4A5B50F711

FASTA73583,275
        10         20         30         40         50         60 
METPDYNTPQ GGTPSAGSQR TVVEDDSSLI KAVQKGDVVR VQQLLEKGAD ANACEDTWGW 

        70         80         90        100        110        120 
TPLHNAVQAG RVDIVNLLLS HGADPHRRKK NGATPFIIAG IQGDVKLLEI LLSCGADVNE 

       130        140        150        160        170        180 
CDENGFTAFM EAAERGNAEA LRFLFAKGAN VNLRRQTTKD KRRLKQGGAT ALMSAAEKGH 

       190        200        210        220        230        240 
LEVLRILLND MKAEVDARDN MGRNALIRTL LNWDCENVEE ITSILIQHGA DVNVRGERGK 

       250        260        270        280        290        300 
TPLIAAVERK HTGLVQMLLS REGINIDARD NEGKTALLIA VDKQLKEIVQ LLLEKGADKC 

       310        320        330        340        350        360 
DDLVWIARRN HDYHLVKLLL PYVANPDTDP PAGDWSPHSS RWGTALKSLH SMTRPMIGKL 

       370        380        390        400        410        420 
KIFIHDDYKI AGTSEGAVYL GIYDNREVAV KVFRENSPRG CKEVSCLRDC GDHSNLVAFY 

       430        440        450        460        470        480 
GREDDKGCLY VCVSLCEWTL EEFLRLPREE PVENGEDKFA HSILLSIFEG VQKLHLHGYS 

       490        500        510        520        530        540 
HQDLQPQNIL IDSKKAVRLA DFDQSIRWMG ESQMVRRDLE DLGRLVLYVV MKGEIPFETL 

       550        560        570        580        590        600 
KTQNDEVLLT MSPDEETKDL IHCLFSPGEN VKNCLVDLLG HPFFWTWENR YRTLRNVGNE 

       610        620        630        640        650        660 
SDIKVRKCKS DLLRLLQHQT LEPPRSFDQW TSKIDKNVMD EMNHFYEKRK KNPYQDTVGD 

       670        680        690        700        710        720 
LLKFIRNIGE HINEEKKRGM KEILGDPSRY FQETFPDLVI YIYKKLKETE YRKHFPQPPP 

       730 
RLSVPEAVGP GGIQS 

« Hide

References

[1]"Analysis and origins of the human and mouse RNase L genes: mediators of interferon action."
Zhou A., Nie H., Silverman R.H.
Mamm. Genome 11:989-992(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C3H/An.
Tissue: Adipose tissue.
[2]"Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action."
Zhou A., Hassel B.A., Silverman R.H.
Cell 72:753-765(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-679.
[3]"The 2-5A/RNase L/RNase L inhibitor (RNI) pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells."
Le Roy F., Bisbal C., Silhol M., Martinand C., Lebleu B., Salehzada T.
J. Biol. Chem. 276:48473-48482(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[4]Erratum
Le Roy F., Bisbal C., Silhol M., Martinand C., Lebleu B., Salehzada T.
J. Biol. Chem. 277:13354-13354(2002)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF281045 mRNA. Translation: AAG33708.1.
L10382 Genomic DNA. Translation: AAA37117.1.
PIRB45771.
RefSeqNP_036012.1. NM_011882.2.
XP_006529588.1. XM_006529525.1.
XP_006529589.1. XM_006529526.1.
XP_006529590.1. XM_006529527.1.
XP_006529591.1. XM_006529528.1.
XP_006529592.1. XM_006529529.1.
XP_006529593.1. XM_006529530.1.
UniGeneMm.259254.

3D structure databases

ProteinModelPortalQ05921.
SMRQ05921. Positions 23-354, 371-708.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ05921.
ChEMBLCHEMBL2687.

PTM databases

PhosphoSiteQ05921.

Proteomic databases

PaxDbQ05921.
PRIDEQ05921.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000086209; ENSMUSP00000083385; ENSMUSG00000066800.
ENSMUST00000182538; ENSMUSP00000138734; ENSMUSG00000066800.
GeneID24014.
KEGGmmu:24014.
UCSCuc007daf.1. mouse.

Organism-specific databases

CTD6041.
MGIMGI:1098272. Rnasel.

Phylogenomic databases

eggNOGCOG0666.
GeneTreeENSGT00750000117792.
HOGENOMHOG000276879.
HOVERGENHBG012673.
InParanoidQ05921.
KOK01165.
OMANMGRNAL.
OrthoDBEOG7VDXNN.
PhylomeDBQ05921.
TreeFamTF344032.

Gene expression databases

ArrayExpressQ05921.
BgeeQ05921.
GenevestigatorQ05921.

Family and domain databases

Gene3D1.25.40.20. 3 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR006567. PUG-dom.
[Graphical view]
PfamPF00023. Ank. 6 hits.
PF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 8 hits.
SM00580. PUG. 1 hit.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 7 hits.
PS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio303947.
PROQ05921.
SOURCESearch...

Entry information

Entry nameRN5A_MOUSE
AccessionPrimary (citable) accession number: Q05921
Secondary accession number(s): Q9ERU7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 11, 2002
Last modified: April 16, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot